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Streams PIS version 3 0 Streams PIS version 3 0 Document Transcript

  • PATIENT INFORMATION SHEET Part 1 Tel: 020 8383 0675 Fax: 020 8383 0584 E-mail: stemcellms@imperial.ac.uk (preferred) Patient Initials: Screening Number: Study Title: Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) Version 3.0 4 August 2013 You are being invited to take part in a research study. Before you decide whether to take part, it is important for you to understand what the research is about, why it is being done and what it will involve. Please take time to read the following information carefully and discuss it with others, if you wish, before making your decision. Do ask us if there is anything that is not clear or if you would like further information. Part 1 tells you about the study and what will happen to you if you agree to take part. Part 2 gives you more detailed information about the conduct of the study. Thank you for taking the time to read this information sheet. We hope you find it helpful. IMPERIAL COLLEGE LONDON Page 1 of 17
  • PATIENT INFORMATION SHEET Part 1 What is the research about? We are looking to see if mesenchymal stem cells (MSCs) can help in the treatment of multiple sclerosis (MS). These are cells that are found in the bone marrow, the spongy tissue found in the middle of most bones. These mesenchymal stem cells have 2 important properties: 1. They can ‘self-renew’ which means that they can multiply to produce greater numbers of themselves. 2. In the presence of tissue inflammation and injury, they can produce soluble factors that reduce the damage and help the tissue to heal. We think that these mesenchymal stem cells may protect the nerves that are damaged in MS. This could happen by: 1. Immunomodulation – the stem cells are thought to reduce or prevent damage to the nervous system by cells of the immune system. 2. Remyelination – the stem cells could help repair the myelin sheath (‘insulation’) around the nerves that have already been damaged. Experiments have suggested that MSCs are useful in preventing inflammation in the nervous system which causes myelin damage. About 2000 people worldwide have been given MSCs for treatment of several different disorders without causing harm. There have also been a few studies using MSCs in MS patients that have been encouraging but all involved small numbers of patients, making it difficult to draw firm conclusions about the safety and benefit of MSC therapy in MS. Where will the research take place? The MS society and the UK Stem Cell Foundation have jointly funded the trial site in London. We will be recruiting 13 patients over 20 months with highly active MS at Imperial College Healthcare NHS Trust (ICHT) for this Phase II study. You will need to be referred to ICHT if you wish to be considered for the trial (please see below). All of the assessments will take place at ICHT but the magnetic resonance imaging (MRI) scans will be performed at the Institute of Neurology, Queen Square. Approximately 15 - 20 similar trials are being run world-wide involving about 160 people in total. Although this trial will run independently, led by Dr Paolo Muraro at ICHT, we will be collaborating with these other international investigators. Your data IMPERIAL COLLEGE LONDON Page 2 of 17
  • PATIENT INFORMATION SHEET Part 1 which includes outcomes of your assessments and MRI scans will also be sent abroad to be analysed. However, all this data will be made anonymous so that you are not identified individually. This is important as we hope that such collaboration will allow us to decide whether mesenchymal stem cells are safe and effective in MS based on the good evidence that can be obtained from larger number of subjects. What will you be looking at? This study has two main aims: 1. We want to know if mesenchymal stem cells taken from an individual and given back to that individual intravenously (via a vein) are safe. 2. We also want to see what effect the mesenchymal stem cells have on the MRI scan of your brain, and in particular whether this treatment reduces the number of inflammatory lesions, a hallmark of active multiple sclerosis, on the scan. However, we will take the opportunity to look for other effects of the MSCs on you – so we will want to regularly examine you and check your bloods. Please see the schedule below for details of your expected commitment. How will the research be done? This is a randomised, double-blind cross-over study. This means that if you are eligible for the trial and wish to take part, then you will be randomly allocated (by a computer) to either the active (mesenchymal stem cells) treatment first followed by the placebo (“dummy”) treatment or vice-versa. After 6 months, the treatments will be reversed. However, neither you nor the doctors involved in the trial will know the order in which you received your treatments. But during the period of the trial, you will receive your MSCs. IMPERIAL COLLEGE LONDON Page 3 of 17
  • PATIENT INFORMATION SHEET Part 1 The diagram below shows what will happen in the trial. First treatment Second treatment What do I have to do? You will first need to be referred to our NHS clinic so that we can decide which trial – if any – is most appropriate for you. This will include consideration for the STREAMS trial but even if you are not eligible for this, then there may be other trials that are suitable for you. If you appear eligible and wish to take part, you will then be formally “screened” for the STREAMS trial because we have to make absolutely sure that you meet a number of criteria for the study. The criteria includes being aged between 18 - 50 years, having a firm diagnosis of MS for between 2 – 10 years and being able to walk at least 20 metres (with or without a walking aid). We also need to have evidence from a MRI scan that you have active MS. IMPERIAL COLLEGE LONDON Page 4 of 17
  • PATIENT INFORMATION SHEET Part 1 If you have received steroids in the last 30 days you will not be able to join the study immediately but you can be considered for participation at a later date. If you meet these criteria at the screening visit, you will be asked to come back to clinic to have a number of procedures (for details please see page 9) including a bone marrow harvest – this involves taking a sample of your bone marrow from your hip bone (please see below for details). These cells are then taken to the laboratory at Hammersmith Hospital to be grown, which takes approximately 4 - 6 weeks. Your cells have to grow to an adequate number in order for us to give them back to you. If your cells do not grow, then you will not be able to continue in the trial. You will then be followed for 12 months during which you will have at least 19 visits to the hospital – more if you notify us of any problems that require us to review you. On several visits, you will have a neurological examination and have blood samples taken. On all visits you will have your vital signs checked – this includes your pulse, blood pressure, and breathing rate. You will have 7 additional visits for the MRIs which take place at the Institute of Neurology over the 12 months. You will also have a total of 3 lumbar punctures and 4 skin tests during the trial. Table 1 below (page 7) is an overview of the visits that will take place in the study and the assessments required. Below the table is a detailed description of each visit which you may find helpful. Do I have to take part? No. It is up to you to decide whether or not to take part. If you do decide to take part, you will be given this information sheet to keep and be asked to sign a number of consent forms. The decision you make will NOT affect the care that you receive now or in the future. What are the alternatives for treatment? There are a number of treatment options in MS which may be more suitable for you. You should not take part in this trial until your doctor has discussed these with you and you feel happy with your decision. What if my care is under another hospital or consultant? If you are not already under our care for your MS, then we require that your GP or neurologist refer you to our MS clinic – the purpose of this visit is that it will allow us to assess your MS in detail and advise you and your GP regarding your MS IMPERIAL COLLEGE LONDON Page 5 of 17
  • PATIENT INFORMATION SHEET Part 1 management and all available clinical trials. This initial NHS visit is NOT part of the study. Eligibility for the STREAMS trial can only be considered at the screening visit – you will be invited to this should you meet the necessary inclusion criteria (please see above). IMPERIAL COLLEGE LONDON Page 6 of 17
  • PATIENT INFORMATION SHEET Part 1 Table 1. Schedule of study assessments and treatments Screening - 10 weeks (±7 days) -8 weeks (±7 days) Informed Consent x x Inclusion/exclusion review x -8 weeks (±7 days) -2 weeks (±14 days) x Week 0 Week 0 Week 4 (±7 days) Week 8 (±7 days) Week 12 (±7 days) Week 16 (±7 days) Week 20 (±7 days) Week 24 (±7 days) Week 24 (±7 days) Week 28 (±7 days) Week 32 (±7 days) Week 36 (±7 days) Week 40 (±7 days) Week 44 (±7 days) Week 48 (±7 days) Week 48 (±7 days) x Medical history x Concomitant medications record x x x x x x x x x x x x x x x x x x x Vital signs x x x x x x x x x x x x x x x x x x x Physical exam x x x x x x x x x Study treatment (MSC) infusion x x x Adverse events record x x Release of MSC product x x x x x x x x x x x x x x x x x x Randomisation x Lumbar puncture x Skin biopsy x Bone marrow harvest x x x EDSS x MSIS29 x x x MSFC x x T25-FW x x x x Quality of life/Fatigue impact scale x x x x Hematology, Blood Chemistry x x x x Blood tests pre-bone marrow harvest x Pregnancy test x x x Urinalysis x x x Research blood samples x Mantoux skin test x x Mantoux readout x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x MRI ECG x x x x x x x x x x x x x IMPERIAL COLLEGE LONDON Page 7 of 17 x
  • PATIENT INFORMATION SHEET Part 1 A Detailed Description of the Study Visits Screening visit: 10 weeks ± 7 days before treatment  During this visit, you will be asked to sign a consent form to enter the study and a consent form to have an MRI. This study MRI will be performed at baseline (0 weeks – see Table 1).  You will be assessed for eligibility for the STREAMS trial.  A full medical and MS history will be taken; we will record any medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood (15mls or 3 teaspoons) will be taken for haematological, clinical chemistry and immunological testing.  Further blood tests (10mls or 2 teaspoons) will include testing for human immunodeficiency virus (HIV) type 1 and 2, Hepatitis B, Hepatitis C, Human T lymphocyte virus (HTLV) 1 and 2, cytomegalovirus (CMV), and syphilis. Please note that testing for HIV and hepatitis B and C will also be required in order to check for pre-existing infections that may affect your safety in this study. You will be appropriately counselled before this blood test to ensure that you understand the implications of a positive test.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) - a member of the clinical team will examine your nervous system to assess how Multiple sclerosis affects you. o Multiple Sclerosis Functional Composite (MSFC) - The MSFC comprises three components: a 9-hole Peg test which assesses eye-hand co-ordination by requiring placement of pegs into 9 holes; the Paced Auditory Serial Addition Test (PASAT) which is a brief test of maths; and a timed 25-feet walk to determine your walking ability. o MSIS-29 questionnaire – The MSIS-29 is a questionnaire consisting of 29 questions about how MS has affected you in the preceding two weeks. o SF-36 questionnaire – This is a questionnaire that asks questions about how MS has affected your quality of life.  A baseline 12 lead ECG will be carried out.  You will be randomly allocated (randomised) to decide the order in which you will receive the MSCs and dummy infusion. If you are eligible, you will then be asked to return within 1 - 3 weeks as a daycase admission to Hammersmith Hospital. Daycase visit: 8 weeks ± 7 days before treatment  At this visit, you will be asked to confirm that you are happy for the tests to continue. IMPERIAL COLLEGE LONDON Page 8 of 17
  • PATIENT INFORMATION SHEET Part 1  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  An Expanded Disability Status Score (EDSS) will be calculated.  Blood samples for research (80mls or approximately 5 tablespoons) will be taken.  Over the day, four procedures will be carried out: - A bone marrow harvest to extract the MSCs will be performed by a clinician experienced in this procedure. This procedure usually takes 20 - 40 minutes. We may insert a cannula (plastic tubing) into your arm and you may need to be given a relaxant or sedation via a vein so that you will not feel pain. It is possible that you may not remember the procedure. Local anaesthetic will be injected around your pelvic bone. A bone marrow aspirate needle will then be inserted into the pelvic bone and bone marrow will be taken in 2 millilitre volumes. (Please also see page 15). - A punch skin biopsy will be taken concurrently with the bone marrow procedure. This requires a small piece (4mm) of skin to be removed. It takes about 5 minutes. This will be done under local anaesthetic. (Please also see page 15). - A lumbar puncture to obtain some cerebrospinal fluid (CSF) - the liquid that bathes the brain and spinal cord - will be performed by a clinician experienced in this procedure and normally takes up to 30 minutes. You will lie on your side, curled up with your knees at your chest, or you will need to sit upright. Your lower back will be cleaned and local anaesthetic will be injected to numb the area. This may sting for a few seconds. Another needle will then be inserted through the numbed skin and into the space between the bones in your back to take a small sample of CSF. You may feel a sensation of pressure. About 20mls (or approximately 1 tablespoon) of CSF will be removed. After the fluid is collected, the needle will be withdrawn. You will be asked to lie flat for two hours and to rest over the next few days. (Please also see page 15). - A Mantoux skin test – this test is normally performed to check whether a person is infected with tuberculosis (TB) but we will use the test to see whether the MSCs alter the result of the test in any way. It involves giving an injection of tuberculin (the protein) very close to the surface of the forearm such that a pale wheal – approximately 6-10mm in diameter - forms. We will record the result of this test 48-72 hours later. (Please also see page 16).  If these procedures are completed successfully, mesenchymal stem cell manufacturing will commence. For your MSCs to be used, they must successfully grow and pass a number of laboratory tests before they are considered suitable and safe to give back to you. IMPERIAL COLLEGE LONDON Page 9 of 17
  • PATIENT INFORMATION SHEET Part 1 Visit: 8 weeks ± 7 days before treatment  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  The Mantoux skin test result will be read.  80mls (or approximately 5 tablespoons) of blood research samples will be taken. Telephone visit: 2 weeks ± 14 days before treatment We will contact you to confirm whether your MSCs can actually be used to treat you. If so, then you will be able to continue in the trial. If not, then you will resume your regular MS care. If your cells have grown, but insufficiently for the trial requirements, then we will store them for you – it may be possible to give them to you at some point in the future assuming it is safe and appropriate to do so. Unused MSCs may also be used for laboratory research unless you request us to destroy them. If the MSCs can be used, you will then be admitted within the next 2 - 4 weeks to receive an infusion. Treatment Daycase visit: Week 0 ± 7 days  An MRI will be carried out prior to infusion of the study treatment.  During this visit, we will check again that you fit the criteria to enter the study and to receive the infusion.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  A Mantoux skin test will be performed.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire  The study treatment will then be infused. Visit: Week 0 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking. IMPERIAL COLLEGE LONDON Page 10 of 17
  • PATIENT INFORMATION SHEET Part 1  You will have your vital signs checked.  An Expanded Disability Status Score (EDSS) will be calculated.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  The Mantoux result will be read. Visit: Week 4 ± 7 days  An MRI will be carried out either on the same day or within 7 days of this visit.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire Visit: Week 8 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  80mls (or approximately 5 tablespoons) of blood research samples will be taken. Visit: Week 12 ± 7 days  An MRI will be carried either on the same day or within 7 days of this visit.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire IMPERIAL COLLEGE LONDON Page 11 of 17
  • PATIENT INFORMATION SHEET Part 1 Visit: Week 16 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  80mls (or approximately 5 tablespoons) of blood research samples will be taken. Daycase Visit: Week 20 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  On the day, a lumbar puncture will be performed by a clinician experienced in this procedure. Treatment Daycase visit: Week 24 ± 7 days  An MRI will be carried out prior to infusion of the study treatment.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  A Mantoux skin test will be performed.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire  The study treatment will then be infused. Visit: Week 24 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  An Expanded Disability Status Score (EDSS) will be calculated.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  The Mantoux skin test result will be read. IMPERIAL COLLEGE LONDON Page 12 of 17
  • PATIENT INFORMATION SHEET Part 1 Visit: Week 28 ± 7 days  An MRI will be carried either on the same day or within 7 days of this visit.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy testing will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire Visit: Week 32 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  80mls (or approximately 5 tablespoons) of blood research samples will be taken. Visit: Week 36 ± 7 days  An MRI will be carried either on the same day or within 7 days of this visit.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire Visit: Week 40 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked. IMPERIAL COLLEGE LONDON Page 13 of 17
  • PATIENT INFORMATION SHEET Part 1  80mls (or approximately 5 tablespoons) of blood research samples will be taken. Daycase Visit: Week 44 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  On the day, a lumbar puncture will be performed by a clinician experienced in this procedure. Visit: Week 48 ± 7 days  A MRI will be carried out.  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will undergo a full physical examination including vital signs.  Blood will be taken for haematological and clinical chemistry testing.  80mls (or approximately 5 tablespoons) of research blood samples will be taken.  Your urine will be tested. A pregnancy test will be performed (if applicable).  A Mantoux skin test will be performed.  A neurological assessment of you and your MS will be carried out. This will include the following: o Expanded Disability Status Score (EDSS) o Multiple Sclerosis Functional Composite (MSFC) o MSIS-29 questionnaire o SF-36 questionnaire Final visit: Week 48 ± 7 days  We will record whether any adverse events have occurred since you were last seen and we will confirm the medications that you are taking.  You will have your vital signs checked.  80mls (or approximately 5 tablespoons) of blood research samples will be taken.  The Mantoux skin test result will be read.  The study will be finished for you at this point IMPERIAL COLLEGE LONDON Page 14 of 17
  • PATIENT INFORMATION SHEET Part 1 Expenses As you will need to visit the hospital more frequently than if you were not taking part in the study, we will reimburse your travel expenses (up to a maximum of £30/visit) to the hospital during the time that you are participating in the study. Please note that as previously stated, the first assessment done to assess your MS under the NHS at Imperial College Healthcare NHS Trust does not form part of the research study and travel expenses cannot be claimed for that outpatient appointment. If you are eligible for patient transportation under the NHS, your referrer or GP will have to authorise and arrange it as per normal NHS practices. What are the side effects of the procedures and the treatment received when taking part? Bone marrow sampling: Bone marrow aspiration is a procedure used to obtain a sample of the liquid part of the bone marrow. The two most common complications that may occur from the procedure are bleeding and infection at the puncture site. The bleeding at the puncture site is usually controlled with external compression with gauze. Local infection at the puncture site is rare but may require oral antibiotics. The procedure is performed under sterile conditions to prevent such infections. Lumbar puncture: A lumbar puncture is a procedure used to obtain cerebrospinal fluid, the liquid that flows inside the nervous system. Side effects from the lumbar puncture include: - Local pain in the lower back: this can occur soon after the procedure and generally settles over 24-48 hours. - Headache: some people experience a headache 24 hours after the procedure that is worse on sitting or standing up. Lying flat for as long as possible after the procedure can minimise the occurrence of this headache. If you do experience a headache, then you should lie flat, drink plenty of fluid and take simple pain-killers. Prolonged headaches, lasting longer than 7 days, develop in only 0.5 - 2 % of people (about 1 in every 50 - 200 patients). These prolonged headaches usually settle within 2 weeks of the lumbar puncture. You should contact us if you are concerned. Skin biopsy: A skin biopsy involves the removal of a small piece of skin tissue, under local anaesthetic, for diagnostic or clinical research purposes. The technique used will be a punch biopsy - this removes a round core from the centre of a specified area of skin. Local anaesthetic is injected and a slight burning sensation may be felt. The biopsy site usually bleeds slightly after the procedure and is held closed either by a stitch which may need to be removed after a few days, or by Steristrip ®, also called IMPERIAL COLLEGE LONDON Page 15 of 17
  • PATIENT INFORMATION SHEET Part 1 ‘paper stitches’. A dressing will be placed over the area. You will be given an information sheet on how to look after the area and the dressing. The biopsy site may feel uncomfortable for one to two days. There is a risk that the biopsy site, especially if not looked after properly, may become infected. You should contact us if you are concerned. A small scar (similar to a chickenpox scar) will form in most cases. Mesenchymal stem cells: Minor side effects of MSCs are as for any transfusion of a cellular product i.e. you might experience fever, chills and rigors. There are, in principle, a number of potential serious side effects related to the known properties of MSC. It is possible that their effects will affect every type of immune response, including those against environmental pathogens such as bacteria, thus exposing you to infections. Furthermore, there is a theoretical risk that MSCs could potentially differentiate into bone, fat, or cartilage in locations where these tissues are not usually found. Finally, there is also the remote possibility that MSCs could form a tumour. However, no significant side effects from intravenous MSC infusions have been reported in the available published series or in several anecdotal accounts. Mantoux skin test: An injection of the tuberculin involves a very superficial injection into the forearm such that a pale, tense wheal – at least 6mm in diameter – forms. If the wheal is less than 6mm, then the test needs to be repeated. Mild irritation, itching or swelling can occur but these are expected. You will need to avoid scratching the site and keep the site clean. Please avoid putting any lotions or creams over the injection site. You will need to return 48-72 hours later to have the result recorded. If you do not come to that appointment, it will mean that the injection will need to be repeated. What about pregnancy? If you are pregnant, breastfeeding or planning to become pregnant, you cannot take part in this study. What are the possible benefits of taking part? You will receive active treatment in this trial if your cells are considered appropriate to infuse. These cells may reduce the activity of the disease but by no means is this a certain outcome. You must be aware that this treatment is experimental and that we are exploring whether this treatment actually benefits people with MS. You must also be aware that there is always the possibility that the treatment could worsen your MS or have any other unwanted side effect. As for any new treatment, the type and probability of risks and side effects cannot be accurately predicted. IMPERIAL COLLEGE LONDON Page 16 of 17
  • PATIENT INFORMATION SHEET Part 1 What happens when the research study stops? Once you have completed the trial, you will continue to be observed within our clinic. The results of the trial will need to be analysed for everyone, which will allow us to know whether MSCs are a safe and beneficial treatment. Once this is established, your doctors will be able to discuss your future treatment with you. What if there is a problem? Any complaint about either the way that you have been treated during the study or possible harm that you may have suffered will be addressed. The details about this process are provided in Part 2 of this information sheet. Will my taking part in the study be kept confidential? All information collected about you during the study will be kept strictly confidential and will be stored on a secure database. You will not be recognisable from your completed questionnaires, as these will only have a study number and initials associated with them. Your name and address will not appear on any study forms that are completed. You will not be identified in any report or publication of the study results. If you decide to take part in the study, we will need to contact your GP and neurologist to tell them about the study. Contact details If you have any more questions, please contact the Principal Investigator, Dr Paolo Muraro or Dr Richard Nicholas on telephone 020 8383 0675. This completes Part 1 of the information sheet. If the information in Part 1 has been of interest and you are considering participating in this study, please continue to read the additional information in Part 2 before making your final decision. IMPERIAL COLLEGE LONDON Page 17 of 17
  • PATIENT INFORMATION SHEET Part 2 Tel: 020 8383 0675 Fax: 020 8383 0584 E-mail: stemcellms@imperial.ac.uk (preferred) Patient Initials: Screening Number: Study Title: Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) Version 3.0 4 August 2013 What if new relevant information becomes available? Sometimes, during the course of a research study, new information becomes available about the treatment that is being studied. If this happens, your research doctor will tell you about it and discuss with you whether you want to continue in the study. If you decide to withdraw, arrangements will be made for your care to continue as it had prior to the study. If you decide to continue in the study, you will be asked to sign an updated consent form to reflect the new information made available to you. What will happen if I don’t want to continue with the study? If you withdraw from the study, we will destroy all your identifiable samples but we will need to use any data collected up to the point of your withdrawal. Your research samples provided – these are labelled only with the study number and do not contain your personal details - will continue to be used for research purposes. You can request in writing that any unused samples that we hold are destroyed. What if there is a problem? We think it is unlikely that you will experience any serious side effects or injury by participating in this research study. Imperial College London holds insurance policies that apply to this study. If you experience serious and lasting harm or injury as a result of taking part in this study, you may be eligible to claim compensation without having to prove that Imperial College is at fault. This does not affect your legal rights to seek compensation. If you are harmed due to someone’s negligence, then you may have grounds for legal action. Regardless of this, if you wish to complain, or have any concerns about any aspect of the way you have been treated during the course of this study then you should immediately inform the Investigators (Dr Paolo Muraro or Dr Richard Nicholas) on 020 8383 0675. IMPERIAL COLLEGE LONDON Page 1 of 3
  • PATIENT INFORMATION SHEET Part 2 The normal National Health Service complaints mechanisms are also available to you. If you are still not satisfied with the response, you may contact the Imperial AHSC Joint Research Office. Will taking part in the study be kept confidential? If you join the study, parts of your medical records and the data collected during the study will be looked at by the study investigators. They may also be looked at by representatives of regulatory authorities and by authorised people from the hospital trust to check that the study is being carried out correctly. All will have a duty of confidentiality to you as a research participant and your identity will not be disclosed outside the research site. In addition, you will not be identified in any report or by publication of the study results. Involvement of the General Practitioner/Family Doctor (GP) If you decide to take part in the study, we will inform your GP and neurologist about your involvement in the study. What will happen to any samples that I give? The blood and some of the spinal fluid samples that will have been taken in the study will be processed in the routine pathology laboratories at the hospital. They will be labelled in accordance with hospital policy. Once the samples have been analysed and the results verified, they will be destroyed according to the routine hospital protocols. For the immunological tests, your blood, spinal fluid and skin biopsy samples will be transferred to a laboratory at Imperial College London (Dr Paolo Muraro) for further analysis in that laboratory or at a collaborating institution. Your samples will be labelled with an identification code. No personal details will be on these samples and no personal information about you will leave the hospital site where the samples were taken. This research has been sanctioned by an ethics committee. If you withdraw from the study, then you will be able to request that such samples be destroyed. However, we will need to use any data obtained up to the point of withdrawal. What will happen to the results of the research study? We plan to publish the results in peer reviewed medical journals and present the data at medical meetings. You will not be identified in any publications relating to the study. If you wish to read any of the publications about the study, you should ask your doctor at your clinic visits to give you a copy. IMPERIAL COLLEGE LONDON Page 2 of 3
  • PATIENT INFORMATION SHEET Part 2 Who is organising and funding the study? The study is being conducted at Imperial Healthcare NHS Hospital Trust and the National Hospital for Neurological and Neurosurgical disease (acquisition and analysis of the MRI scans). The anonymised MRI data will be sent to a centralised image analysis facility (in Basel, Switzerland) and the data collected from the clinic visits, also anonymised, to a central clinical research organisation (in Genova, Italy). This will allow all the results from the separate ongoing trials to be pooled to allow meaningful conclusions to be drawn – something that will not be possible with smaller, individual studies. Our study is being jointly funded by two charities: the UK Multiple Sclerosis Society and the UK Stem Cell Foundation. Who has reviewed the study? The study has been reviewed by other doctors who are experts in the field of multiple sclerosis and its treatment. This study was passed by the Gene Therapy Advisory Committee (GTAC). The study has also been reviewed and approved by the Medicines and Healthcare Products Regulatory Agency (MHRA). Please take your time to think about this trial. Remember that your participation is entirely voluntary. You are entitled to drop out if you so wish without prejudicing further treatment. You are also entitled to keep a copy of this information leaflet and the accompanying questions and answers. If you have any more questions, please contact Dr Paolo Muraro or Dr Richard Nicholas on 020 8383 0675. IMPERIAL COLLEGE LONDON Page 3 of 3
  • VERSION 3.0 4 AUGUST 2013 Patients Initials PATIENT CONSENT FORM Screening Number Study Title: Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) Please initial each statement below to indicate your consent. Initials I confirm that I have read and understood the Patient Information Sheet Version 3.0 dated 4 August 2013 for the above study. I consent to my GP and/or neurologist being informed of my participation in this study. I give my permission for my personal information to be held by NHS staff involved in this clinical trial and to be able to share this information with other healthcare professionals. I understand that the regulatory authorities may need to review my medical notes in the future as part of audit/licensing. I agree to my details, including patient identifiable information, being stored on secure, encrypted Imperial College London computer systems I give permission that my anonymised data be sent abroad for analysis as part of the international collaborative effort. I give my permission for blood samples to be collected and tested during the trial to monitor haematological, biochemical and immunological parameters during treatment. I give permission that my blood is tested for HIV and Hepatitis B and C. I understand why these tests are being performed and have been adequately counselled about the implications of a positive test. I give permission for bone marrow sampling to obtain stem cells to be used as part of this trial. I agree that if my stem cells do not grow adequately for the trial then they could still be stored for future potential use by myself. I consent to any unused bone marrow or stem cell samples being used for laboratory research related to this study. IMPERIAL COLLEGE LONDON Page 1 of 2
  • VERSION 3.0 4 AUGUST 2013 PATIENT CONSENT FORM I give permission for a lumbar puncture to be performed on three occasions as part of this study. I am aware of the potential side effects. I consent to any unused spinal fluid samples being used for laboratory research related to this study. I give permission for a skin biopsy to be carried out as part of this study. I am aware of the potential side effects. I give permission that a Mantoux skin test be performed as part of this study and understand that I need to attend for the readout. I give my permission for my collected fluid samples to be used for study-related laboratory research sanctioned by the ethics committee. I agree that unused blood samples and a DNA sample will be stored for potential future research use. However, no additional testing will be undertaken unless sanctioned by an ethics committee. I understand that I am free to withdraw from the study at any time without having to give a reason for the withdrawal and without prejudicing any future medical care. If I withdraw, I give permission for information collected about me and the results of any investigations to be retained up to that date. Any results from the study-related laboratory tests will also be used. Any stored, unused fluid samples can continue to be used for such research but will be destroyed if I request this in writing. I have been given the opportunity to ask questions and discuss this study and I have received satisfactory answers to all my questions. I agree to take part in this study. Patients’ signature................................................... Date................................... (NAME IN BLOCK CAPITALS)……..................................................…………….. Investigator’s signature........................................... Date: ................................ (NAME IN BLOCK CAPITALS).........................................………………………… One original signed and dated copy of the Patient information sheet/Consent form is to be given to the patient, one is to be kept in the patient notes and one in the investigator site file. IMPERIAL COLLEGE LONDON Page 2 of 2
  • VERSION 2.0 4 AUGUST 2013 LETTER TO PATIENT’S GP Hospital headed paper Date Dr Address Dear Dr Re: [Patient name] Study Title: Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) Your patient has recently agreed to participate in the above study that is taking place at <Insert Hospital site>. This trial aims to determine whether mesenchymal stems cells, derived from an and given back to that person, are safe and whether they have any effect on Resonance Imaging assessed activity in Multiple sclerosis. It will also determine on the clinical and immunological course of the disease over a 1-year time-period. the study are outlined in the enclosed patient information sheet. individual Magnetic the effect Details of The trial has been approved by the Gene Therapy Advisory Committee (GTAC). If you require any further information about the study, please do not hesitate to contact me on: Tel: 020 8383 0675 Fax: 020 8383 0584 E-mail: stemcellms@imperial.ac.uk Please file this letter in the patient’s notes. I would appreciate being notified if he/she is no longer one of your patients. Many thanks for your help. Yours sincerely Consultant Neurologist Enc: Patient Information Sheet and Consent IMPERIAL COLLEGE LONDON Page 1 of 1
  • VERSION 2.0 4 AUGUST 2013 LETTER TO PATIENT’S NEUROLOGIST Hospital headed paper Date Dr Address Dear Dr Re: [Patient name] Study Title: Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) Your patient has recently agreed to participate in the above study that is taking place at <Insert Hospital site>. This trial aims to determine whether mesenchymal stems cells, derived from an and given back to that person, are safe and whether they have any effect on Resonance Imaging assessed activity in Multiple sclerosis. It will also determine on the clinical and immunological course of the disease over a 1-year time-period. the study are outlined in the enclosed patient information sheet. individual Magnetic the effect Details of The trial has been approved by the Gene Therapy Advisory Committee (GTAC). If you require any further information about the study, please do not hesitate to contact me on: Tel: 020 8383 0675 Fax: 020 8383 0584 E-mail: stemcellms@imperial.ac.uk Please file this letter in the patient’s notes. I would appreciate being notified if he/she is no longer one of your patients. Many thanks for your help. Yours sincerely Consultant Neurologist Enc: Patient Information Sheet and Consent IMPERIAL COLLEGE LONDON Page 1 of 1